New hydrogen atom transfer methodologies for synthesis

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Abstract

This thesis describes the development of new hydrogen atom transfer (HAT) methodologies, particularly focussed on additions to the C≡N bond (an underutilised radical acceptor). The two main published bodies of work are outlined below in Scheme 1 and 2. A HAT-mediated intramolecular C-C coupling reaction between alkenes and nitriles, using PhSiH3 and catalytic Fe(acac)3, has been established.1 This introduces a new strategic bond disconnection for ring-closing reactions, forming ketones via imine intermediates. Of note is the scope of the reaction, including formation of sterically hindered ketones, spirocycles and fused aliphatic systems. Inspired by aspects of the alkene-nitrile project, a radical domino cyclisation reaction of N-cyanamide alkenes, mediated by HAT was also developed (Scheme 2).2 This methodology, using PhSiH3 and catalytic Fe(acac)3, allows for the synthesis of challenging (spiro)quinazolinone scaffolds from simple, tractable (hetero)aryl carboxylic acid and cyanamide building blocks. Further studies, such as exploiting unexpected side-reactions, as well as probing curious mechanistic observations have been made throughout this work. Possible future work is suggested throughout this thesis and hopefully can be pursued in the near future.

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Previously held under moratorium in Chemistry Department (GSK) from 17/06/2020 until 22/11/2022
The confidentiality statement on each page of this thesis DOES NOT apply

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